Diclofenac/misoprostol: the European clinical experience

The fixed combination of diclofenac sodium and misoprostol (Arthrotec) is the only nonsteroidal antiinflammatory drug (NSAID) that contains a gastroprotective component and is available in 2 formulations:(1) an enteric coated core of diclofenac sodium 50 mg surrounded by a mantle of misoprostol 200 microg, and (2) a 75 mg enteric coated diclofenac core also surrounded by a 200 microg mantle of misoprostol. This article reviews the European clinical experience with both formulations in patients with arthritis.

Three randomized, blinded, multicenter studies, including one in general practice, evaluated the efficacy of combination diclofenac/misoprostol versus diclofenac or ibuprofen in a total of 1824 patients with rheumatoid arthritis (RA) or osteoarthritis (OA). Four additional studies assessed antiarthritic efficacy and employed endoscopy to compare the gastroduodenal safety of combined diclofenac50/misoprostol with that of diclofenac, naproxen, piroxicam, or indomethacin in 1459 patients with RA, OA, or ankylosing spondylitis. The gastroduodenal safety and antiarthritic efficacy of diclofenac75/misoprostol was compared with that of diclofenac in one endoscopy study involving 514 patients with RA or OA.

The efficacy and safety data obtained from these European clinical trials show that both formulations diclofenac50/misoprostol and diclofenac75/misoprostol are effective antiinflammatory drugs, with clinical efficacy equivalent to that of diclofenac. Diclofenac50/misoprostol is at least as effective as naproxen, piroxicam, indomethacin, and ibuprofen. Both formulations of the combination were associated with significantly fewer gastroduodenal ulcers compared with diclofenac. In separate studies, the tolerability of diclofenac50/misoprostol (as determined by withdrawal rates) was shown to be equivalent to that of diclofenac, naproxen, piroxicam, and ibuprofen, and the tolerability of diclofenac75/misoprostol was shown to be equivalent to that of diclofenac. The diclofenac50/misoprostol was associated with fewer decreases in hemoglobin concentration compared with diclofenac in the general practice study as well as in hospital patients.

Diclofenac50/misoprostol and diclofenac75/misoprostol are effective in treating the signs and symptoms of RA and OA and are well tolerated by the majority of patients. Both of these formulations achieve a significant reduction in the incidence of both gastric and duodenal ulcers compared with other NSAID.